This K0I application is to support career development for a new investigator to gain knowledge and skills in conducting multi-disciplinary research on diabetes etiology. Type 2 diabetes (T2D) is a major cause of morbidity and mortality in the United States and many other countries. Dietary intake has been suggested to play an important role in the etiology of T2D. However, the evidence is inconsistent, particularly regarding protective dietary factors, such as omega 3 fatty acids, isoflavones and antioxidants. A reason for inconsistencies in results may be due to the failure to consider individual host response to dietary intake. Cumulative evidence has suggested an important role of gene-diet interaction in the etiology of T2D. Data from laboratory studies have suggested that isoflavones, abundant in legumes and soy products, and eicosapentaenoic acid, abundant in fish oils, activate PPAR gene expression. Physical activity, a protective factor for T2D, has been shown to interact with PPAR and PGC1 genes in the development of T2D in observational and intervention studies. In this K01 application, the candidate proposes to investigate the role of PPAR and PGC1 genes and their interaction with dietary intake and physical activity on diabetes risk. These two related families of genes were selected because of their important role on energy balance and insulin resistance. Data from an on-going genome wide association study (GWAS) of 880 T2D cases and 1500 controls will be used to screen promising SNPs. A replication study will be performed using an independent set of 1500 T2D cases and 1500 matched controls. Gene-diet and gene-physical activity interactions will be evaluated in a combined set of screening and replication phase participants. The knowledge gained from the study will have a significant public health impact on prevention and individualized treatment of T2D. Of equal importance, through this award and research application, the candidate will gain new knowledge and skills in conducting molecular epidemiological study that will facilitate her achieving her career goals, i.e., to become an independent researcher in T2D.